On June 22, 2020 Ascendis Pharma A/S (Nasdaq: ASND), a biopharmaceutical company that utilizes its innovative TransCon technologies to address unmet medical needs, reported the presentation of preclinical data for TransCon IL-2 β/γ, an oncology product candidate designed to provide sustained systemic release of a receptor-biased IL-2 (IL-2 β/γ), at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II from June 22 to June 24, 2020 (Press release, Ascendis Pharma, JUN 22, 2020, View Source [SID1234561294]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Our preclinical results have demonstrated that TransCon IL-2 β/γ selectively binds and activates the IL-2 β/γ receptor and provides sustained and long-lasting exposure. By applying our TransCon technology to this clinically validated cytokine, we have overcome the two most significant limitations of IL-2 therapy, improving both the receptor-binding properties and the pharmacokinetic profile," said Juha Punnonen, M.D., Ph.D., Ascendis Pharma’s Senior Vice President and Head of Oncology. "Based on the promising preclinical results we’ve seen with our TransCon IL-2 β/γ and TransCon TLR7/8 Agonist product candidates, we believe our TransCon technologies – which enable systemic and long-acting intratumoral administration – have the potential to improve treatment outcomes in cancer patients. We look forward to our first Investigational New Drug application, or similar, in oncology later this year for TransCon TLR7/8 Agonist, followed by a planned filing for TransCon IL-2 β/γ in 2021."

TransCon IL-2 β/γ is a novel long-acting prodrug of IL-2 β/γ designed to address limitations of alternative IL-2 treatments, including aldesleukin, which has been available since the 1990’s as a treatment for advanced kidney cancer and advanced melanoma. TransCon IL-2 β/γ is designed with a parent drug that selectively binds and activates the IL-2Rβ/γ. By applying the innovative TransCon technology platform, preclinical data also showed that TransCon IL-2 β/γ demonstrated a long in vivo half-life of approximately 32 hours, expected to support potential dosing of every three weeks in patients. Preclinical results show a single dose of TransCon IL-2 β/γ selectively expanded lymphocyte counts (CD8+ T cells and NK cells) in non-human primates, with minimal signs of systemic inflammation (IL-5 and IL-6 markers) or endothelial cell damage (E-Selectin and VCAM-1 markers) and no dose-limiting toxicities.

Presentation Details

American Association of Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II

Title Date/Time
P4507: TransCon IL-2 β/γ: a novel long-acting prodrug of receptor-biased IL-2 designed for improved pharmocokinetics and optimal activation of T cells for the treatment of cancer Monday, June 22, 2020

8:45 a.m. Eastern

The poster is available on the company’s website under Selected Publications in the Pipeline section:

View Source

About TransCon Oncology Programs

Ascendis Pharma is developing potentially best-in-class oncology therapies by applying its TransCon technologies for systemic and intratumoral administration to clinically validated pathways in order to improve efficacy and reduce systemic toxicity. Multiple oncology programs are currently in preclinical evaluation.

About TransCon Technology

TransCon refers to "transient conjugation." The proprietary TransCon platform is an innovative technology to create new therapies that are designed to potentially optimize therapeutic effect, including efficacy, safety and dosing frequency. TransCon molecules have three components: an unmodified parent drug, an inert carrier that protects it, and a linker that temporarily binds the two. When bound, the carrier inactivates and shields the parent drug from clearance. When injected into the body, physiologic conditions (e.g., pH and temperature) initiate the release of the active, unmodified parent drug in a predictable manner. Because the parent drug is unmodified, its original mode of action is expected to be maintained. TransCon technology can be applied broadly to a protein, peptide or small molecule in multiple therapeutic areas, and can be used systemically or locally.

On June 22, 2020 AIMM, a privately-held biopharmaceutical company, reported it has presented preclinical data at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2020 Virtual Annual Meeting from its antibody programs in oncology using a rich pipeline of tumor- specific antibodies from cured cancer patients (Press release, AIMM Therapeutics, JUN 22, 2020, View Source [SID1234561293]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Recognizing that cured cancer patients have benefited, directly or indirectly, from a robust and specific antibody response, AIMM has set out to select those functional antibodies as a starting point for its drug development programs," said John Womelsdorf, Ph.D., chief executive officer of AIMM Therapeutics. "AIMM is perfectly positioned to advance this approach; firstly, through our ability to interrogate the entire B cell repertoire of the surviving patient and identify novel targets and anti-cancer antibodies using our AIMSelect platform. And, secondly, we are able to potentiate these antibodies for use as therapies through our AIMProve platform to leverage the unique biology that was underlying the original donor’s successful clinical response."

AIMM has a pipeline of multiple drug candidates that bind to novel cancer targets and epitopes. The company’s lead asset, AT1412, is a CD9-targeted antibody derived from a stage 4 melanoma patient with brain metastasis who was successfully treated with autologous T-cell based immunotherapy and is still tumor-free after 13 years despite having an aggressive cancer. AT1412 is going through the last stages of preclinical development for B-cell lymphoblastic leukemia/lymphoma (B-ALL) and CD9+ solid tumors, such as melanoma, gastric, breast, and esophageal cancers. Preclinical data from studies of AT1412 in B-ALL and melanoma tumor models show monotherapy treatment induced full tumor rejection that in the case of melanoma can be further sustained in combination with nivolumab. Two posters presented at AACR (Free AACR Whitepaper) demonstrate the potential for AT1412 to be a potent antibody capable of inducing cell death and facilitating the trafficking of immune cells into the tumor microenvironment.

Additionally, several antibody candidates, such as CD3-bispecific/ADC/CAR-T assets, are in lead optimization and could provide for multiple non-dilutive partnering opportunities and co-development collaborations. AT1413, isolated from an M5 acute myeloid leukemia patient that underwent allograft stem cell transplantation, has the potential to be formatted into a CD3-bispecific, ADC or CAR-T. Another poster presented at AACR (Free AACR Whitepaper) describes two different bispecific T-cell engaging forms of AT1413 that induce strong anti-tumor cytotoxic activities in AML and solid tumors like melanoma and breast carcinoma. A fourth poster presented at the AACR (Free AACR Whitepaper) annual meeting reviews AT1636, an antibody targeting a cancer- specific glyco-modified antigen, which was retrieved from a patient with Lynch syndrome.

Hans van Eenennaam, Ph.D., who joined AIMM Therapeutics in 2019 as its chief scientific officer and is credited as a co-inventor of pembrolizumab, added, "Using patient-derived antibodies as therapeutics represents an exciting approach to drug development because they are unlocking novel targets and mechanisms of action. As exemplified by our AT1412 (anti-CD9 antibody), we have identified that this patient-derived antibody induces antibody-mediated tumor kill and promotes immune cell penetration into the tumor. Our technologies were initially developed and validated for applications in infectious disease, resulting in the out licensing of a product candidate for respiratory syncytial virus to MedImmune that is now in Phase 3 development. Following years of groundbreaking experience in the field led by my predecessor and founder of the company Hergen Spits, professor at the Academic Medical Center in Amsterdam, we are now applying our evolved and highly selective antibody technologies to treat cancer. Our unique and proprietary technology allows us to interrogate every memory B-cell in both human blood and tumors for anti-cancer reactivity. Together with our rich tradition of cutting-edge immunology, we are uniquely positioned to identify targets on both hematological and solid tumors that have not been previously identified before."

AACR Presentations on June 22, 2020
Poster 531, Session: Antibody Technologies
AT1412, a patient-derived antibody in development for the treatment of cd9-positive precursor b-acute lymphoblastic leukemia

Poster 532, Session: Antibody Technologies
A patient-derived anti-CD9 antibody induces tumor rejection and synergistically enhances anti-PD1 activity

Poster 542, Session: Antibody Technologies
T-cell engager bispecific formats of an AML patient-derived antibody targeting a unique sialylated CD43 epitope induce kill of melanoma cells in vitro and in vivo

Poster 5163, Session: Antibody Technologies
A colon cancer survivor-derived antibody recognizes a previously unidentified truncated, O-mannosylated 70kDa variant of E-cadherin

On June 22, 2020 Agenus Inc. (NASDAQ: AGEN), an immuno-oncology company with an extensive pipeline of checkpoint antibodies, cell therapy, adjuvants, and vaccines designed to activate immune response to cancers and infections, reported that it will make a scientific presentation today on optimal anti-cancer combinations with Fc enhanced anti-CTLA-4, AGEN1181, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2020 Virtual Annual Meeting (Press release, Agenus, JUN 22, 2020, View Source [SID1234561292]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"AGEN1181 is an Fc-engineered anti-CTLA-4 that has shown exciting clinical activity in an early phase 1 clinical trial, which was recently presented at ASCO (Free ASCO Whitepaper)," said Dr. Antoine Tanne, Lead Scientist, Agenus Immune Biology Team. "Today, at AACR (Free AACR Whitepaper), we report that combinations with AGEN1181 demonstrate curative responses in preclinical models resistant to anti-PD-1. These data illustrate the potential of combining allogeneic cell therapies with checkpoint antibodies, such as AGEN1181, to deliver curative benefit in difficult to treat settings."

Title: "Expanding the therapeutic potential of anti-PD-1 and anti-CTLA-4 therapy with innovative Fc engineering and rationale combinations for the treatment of solid tumors"
Presenter: Antoine J. Tanne. Ph.D
Abstract: 922 / 24
Session: Combination Immunotherapies 1
Date/Time: June 22, 2020, 9am-6pm

Presentations will be available for on-demand viewing online at View Source!/9045/sessions/@sessiontype=Virtual%20Symposium/1

On June 22, 2020 MacroGenics, Inc. (NASDAQ: MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, reported presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II, taking place June 22-24, 2020 (Press release, MacroGenics, JUN 22, 2020, View Source [SID1234561287]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are pleased to present data at this year’s AACR (Free AACR Whitepaper) that highlight three platform technologies upon which multiple molecules are being developed at MacroGenics. We are presenting preclinical data for MGC018, our investigational antibody-drug conjugate targeting B7-H3, that provide evidence for an immune-mediated anti-tumor mechanism, as well as a rationale for clinical investigation of this molecule in combination with checkpoint blockade. Separately, we are presenting data from our novel Fc-engineered, bispecific DART molecule that binds CD25 and CTLA-4 that is capable of depleting tumor-infiltrating regulatory T cells with high specificity in vitro," said Ezio Bonvini, M.D., Senior Vice President and Chief Scientific Officer of MacroGenics. "Finally, one of the clinical investigators for flotetuzumab, our investigational CD123 x CD3 DART molecule, will be presenting preclinical data from his research with this molecule during an oral Education Session."

AACR II Presentations

MGC018, a duocarmycin-based antibody-drug conjugate targeting B7-H3, exhibits immunomodulatory activity and enhanced antitumor activity in combination with checkpoint inhibitors

Poster Session: PO.ET07.01 – Cell Surface Antigens and Receptors as Drug Targets

MGC018 is an investigational antibody-drug conjugate targeting B7-H3 that has shown preliminary anti-tumor activity in an ongoing Phase 1 dose escalation study in patients with advanced solid tumors. The poster presented at AACR (Free AACR Whitepaper) describes preclinical data suggesting that MGC018 can promote immune surveillance or stimulate immune responses to dying cancer cells that led to immunological memory, and when combined with checkpoint blockade may enhance anti-tumor activity.

These studies used a mouse model system designed to evaluate anti-tumor activity in an intact and functioning immune system. In this in vivo model, MGC018 demonstrated targeted activity against tumors expressing human B7-H3. Mechanistically, in vitro data suggested that MGC018 induced immunogenic cell death of target cells with the translocation of calreticulin to the cell surface during apoptosis. In addition, treatment with MGC018 in this model system led to an increased infiltration of T cells into the tumor microenvironment. Depleting these T cells attenuated the anti-tumor activity by MGC018, demonstrating their role in mediating response. Furthermore, MGC018 combined with an anti-PD-1 antibody enhanced anti-tumor activity observed in this study. Finally, mice that had achieved a complete response to initial treatment with MGC018 with or without checkpoint blockade survived longer when re-challenged with tumor without subsequent treatment compared to mice that had not received treatment with MGC018, suggesting immunological memory.

Investigational CD25 x CTLA-4 bispecific DART molecule for depletion of tumor infiltrating Tregs via an enhanced Fc-dependent effector mechanism

Poster Session: PO.IM02.23 – Therapeutic Antibodies 1

The poster presented at AACR (Free AACR Whitepaper) described a preclinical bispecific CD25 x CTLA-4 DART molecule containing an Fc region engineered to enhance clearance of target cells by antibody-dependent cellular cytotoxicity. This molecule was designed to deplete tumor-associated regulatory T cells co-expressing CD25 and CTLA-4 to reduce immune suppression mediated by these cells but preserve effector T cell function. CD25 is the alpha subunit of IL-2 receptor and CTLA-4 is a molecule involved in regulatory T cell function.

In vitro studies showed that the Fc-engineered bispecific CD25 x CTLA-4 DART molecule depleted regulatory T cells, with minimal effect on effector T cells. This depletion of regulatory T cells was shown to occur through an Fc-dependent mechanism, as a control CD25 x CTLA-4 DART molecule with an inactivated Fc domain had no effect in this assay. In addition, the bispecific CD25 x CTLA-4 DART molecule preserved cytotoxic T cell effector function in vitro compared to a combination of Fc-engineered monoclonal antibodies independently targeting CD25 and CTLA-4.

Immune escape after bone marrow transplantation: Hiding in plain sight

Educational Session: ED52 – Immunotherapy, Immune Evasion in Myeloid Malignancies, and Therapeutic Implications

John F. DiPersio, M.D., Ph.D., from Washington University School of Medicine in St. Louis, will present an overview of his research related to immune evasion and mechanisms of relapse after allogeneic hematopoietic cell transplantation (allo-HCT). The presentation will include preclinical data on flotetuzumab (MGD006), an investigational CD123 x CD3 bispecific DART molecule, suggesting a potential role for this molecule in treating patients with acute myeloid leukemia whose disease is relapsing after allo-HCT.

Date: June 24, 2020
Time: 5:30 – 5:50pm ET
Location: AACR (Free AACR Whitepaper) Virtual Annual Meeting II at www.aacr.org

The posters will be available on the Events & Presentations page on MacroGenics’ website at View Source

On June 22, 2020 CytomX Therapeutics, Inc. (Nasdaq: CTMX) reported that its partner Bristol Myers Squibb presented preclinical data from BMS-986249 and BMS-986288, anti-CTLA-4 Probody therapeutics generated with CytomX’s novel Probody technology platform (Press release, CytomX Therapeutics, JUN 22, 2020, View Source [SID1234561285]). The electronic poster #4551 titled "Preclinical characterization of novel anti-CTLA-4 prodrug antibodies with an enhanced therapeutic index" was presented as part of the Therapeutic Antibodies 3 Session at the American Association of Cancer Research’s (AACR) (Free AACR Whitepaper) 2020 Virtual Annual Meeting II.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

BMS-986249 is a Probody version of the anti-CTLA-4 antibody ipilimumab (Yervoy). In February 2020, Bristol Myers Squibb treated the first patient in a Part 2a randomized cohort expansion in an ongoing Phase 1/2a trial of BMS-986249 in combination with Opdivo (nivolumab) in patients with metastatic melanoma. Additional information is available at ClinicalTrials.gov using the Identifier NCT03369223.

BMS-986288 is a Probody of a nonfucosylated version of ipilimumab (anti-CTLA-4 NF). In September 2019, Bristol Myers Squibb initiated the dose escalation phase of a Phase 1/2a clinical trial of BMS-986288 administered as monotherapy and in combination with nivolumab in patients with selected advanced solid tumors. Additional information is available at ClinicalTrials.gov using the Identifier NCT03994601.

These Probody programs, designed to optimize the therapeutic index of CTLA-4-directed therapy, arose from the companies’ 2014 worldwide oncology license and collaboration agreement.

"This important work within our Bristol Myers Squibb alliance is aimed at broadening the utility of this foundational immunotherapeutic approach to the treatment of cancer," said Sean McCarthy D.Phil., president, chief executive officer and chairman of CytomX Therapeutics. "We look forward to seeing the full potential of these programs as they continue to advance in the clinic."